Core outcome sets for trials of interventions to prevent and to treat multimorbidity in adults in low and middle-income countries: the COSMOS study

ABSTRACT Introduction The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs. Methods To generate a comprehensive list of relevant prevention and treatment outcomes, we conducted a systematic review and qualitative interviews with people with multimorbidity and their caregivers living in LMICs. We then used a modified two-round Delphi process to identify outcomes most important to four stakeholder groups (people with multimorbidity/caregivers, multimorbidity researchers, healthcare professionals and policymakers) with representation from 33 countries. Consensus meetings were used to reach agreement on the two final COS. Registration: https://www.comet-initiative.org/Studies/Details/1580. Results The systematic review and qualitative interviews identified 24 outcomes for prevention and 49 for treatment of multimorbidity. An additional 12 prevention and 6 treatment outcomes were added from Delphi round 1. Delphi round 2 surveys were completed by 95 of 132 round 1 participants (72.0%) for prevention and 95 of 133 (71.4%) participants for treatment outcomes. Consensus meetings agreed four outcomes for the prevention COS: (1) adverse events, (2) development of new comorbidity, (3) health risk behaviour and (4) quality of life; and four for the treatment COS: (1) adherence to treatment, (2) adverse events, (3) out-of-pocket expenditure and (4) quality of life. Conclusion Following established guidelines, we developed two COS for trials of interventions for multimorbidity prevention and treatment, specific to adults in LMIC contexts. We recommend their inclusion in future trials to meaningfully advance the field of multimorbidity research in LMICs. PROSPERO registration number CRD42020197293.


Background and Objectives 2a
Describe the background and explain the rationale for developing the COS.Describe the rationale for stakeholder groups involved in the COS development process, eligibility criteria for participants from each group, and a description of how the individuals involved were identified.

5-7, in different stages
Information Sources 6a Describe the information sources used to identify an initial list of outcomes.Present data on the number and relevant characteristics of the people involved at all stages of COS development.

Outcomes 13a
List all outcomes considered at the start of the consensus process.
Table 3 13b Describe any new outcomes introduced and any outcomes dropped, with reasons, during the consensus process.9, also Table 3 COS 14 List the outcomes in the final COS. 1 (Abstract), 10 (Results), also 16 (afghanistan or albania or algeria or american samoa or angola or "antigua and barbuda" or antigua or barbuda or argentina or armenia or armenian or aruba or azerbaijan or bahrain or bangladesh or barbados or republic of belarus or belarus or byelarus or belorussia or byelorussian or belize or british honduras or benin or dahomey or bhutan or bolivia or "bosnia and herzegovina" or bosnia or herzegovina or botswana or bechuanaland or brazil or brasil or bulgaria or burkina faso or burkina fasso or upper volta or burundi or urundi or cabo verde or cape verde or cambodia or kampuchea or khmer republic or cameroon or cameron or cameroun or central african republic or ubangi shari or chad or chile or china or colombia or comoros or comoro islands or iles comores or mayotte or democratic republic of the congo or democratic republic congo or congo or zaire or costa rica or "cote d'ivoire" or "cote d' ivoire" or cote divoire or cote d ivoire or ivory coast or croatia or cuba or cyprus or czech republic or czechoslovakia or djibouti or french somaliland or dominica or dominican republic or ecuador or egypt or united arab republic or el salvador or equatorial guinea or spanish guinea or eritrea or estonia or eswatini or swaziland or ethiopia or fiji or gabon or gabonese republic or gambia or "georgia (republic)" or georgian or ghana or gold coast or gibraltar or greece or grenada or guam or guatemala or guinea or guinea bissau or guyana or british guiana or haiti or hispaniola or honduras or hungary or india or indonesia or timor or iran or iraq or isle of man or jamaica or jordan or kazakhstan or kazakh or kenya or "democratic people's republic of korea" or republic of korea or north korea or south korea or korea or kosovo or kyrgyzstan or kirghizia or kirgizstan or kyrgyz republic or kirghiz or laos or lao pdr or "lao people's democratic republic" or latvia or lebanon or lebanese republic or lesotho or basutoland or liberia or libya or libyan arab jamahiriya or lithuania or macau or macao or "macedonia (republic)" or macedonia or madagascar or malagasy republic or malawi or nyasaland or malaysia or malay federation or malaya federation or maldives or indian ocean islands or indian ocean or mali or malta or micronesia or federated states of micronesia or kiribati or marshall islands or nauru or northern mariana islands or palau or tuvalu or mauritania or mauritius or mexico or moldova or moldovian or mongolia or montenegro or morocco or ifni or mozambique or portuguese east africa or myanmar or burma or namibia or nepal or netherlands antilles or nicaragua or niger or nigeria or oman or muscat or pakistan or panama or papua new guinea or new guinea or paraguay or peru or philippines or philipines or phillipines or phillippines or poland or "polish people's republic" or portugal or portuguese republic or puerto rico or romania or russia or russian federation or ussr or soviet union or union of soviet socialist republics or rwanda or ruanda or samoa or pacific islands or polynesia or samoan islands or navigator island or navigator islands or "sao tome and principe" or saudi arabia or senegal or serbia or seychelles or sierra leone or slovakia or slovak republic or slovenia or melanesia or solomon island or solomon islands or norfolk island or norfolk islands or somalia or south africa or south sudan or sri lanka or ceylon or "saint kitts and nevis" or "st.kitts and nevis" or saint lucia or "st.lucia" or "saint vincent and the grenadines" or saint vincent or "st.

Pakistan
Good quality medicines should be provided and used before, during and after treatment for both rich and poor without any discrimination.

Healthcare quality
Peru I would hope the best not, to be able to live normal, to be able to make normal life.
Health-related quality of life Peru the CT scan was one hundred [soles] and so many, and the other was almost 300 soles, so at that time I did not have… Healthcare cost Suriname She does not want additional medication prescribed or that the doses be increased.

Suriname
Physical therapist taught me was to accept my disabilities.It was hard because I realized that my life would never be the same.

Acceptance of illness
Appendix

4 3b 4 3c
condition(s) and population(s) covered by the COS.Describe the intervention(s) covered by the COS.Describe the setting(s) in which the COS is to be applied

Table 3
vincent" or grenadines or sudan or suriname or surinam or dutch guiana or netherlands guiana or syria or syrian arab republic or tajikistan or tadjikistan or tadzhikistan or tadzhik or tanzania or tanganyika or thailand or siam or timor leste or east timor or togo or togolese republic or tonga or "trinidad and tobago" or trinidad or tobago or tunisia or turkey or "turkey (republic)" or turkmenistan or turkmen or uganda or ukraine or uruguay or uzbekistan or uzbek or vanuatu or new hebrides or venezuela or vietnam or viet nam or middle east or west bank or gaza or palestine or yemen or yugoslavia or zambia or zimbabwe or northern rhodesia or global south or africa south of the sahara or sub-saharan africa or subsaharan africa or africa, central or central africa or africa, northern or north africa or northern africa or magreb or maghrib or sahara or africa, southern or southern africa or africa, eastern or east africa or eastern africa or africa, western or west africa or western africa or west indies or indian ocean islands or caribbean or central america or latin america or "south and central america" or south america or asia, central or central asia or asia, northern or less developed world or lesser developed countr* or lesser developed nation?or lesser developed population?or lesser developed world or under developed countr* or under developed nation?or under developed population?or under developed world or underdeveloped countr* or underdeveloped nation?or underdeveloped population? or underdeveloped world or middle income countr* or middle income nation?or middle income population?or low income countr* or low income nation?or low income population?or lower income countr* or lower north asia or northern asia or asia, southeastern or southeastern asia or south eastern asia or southeast asia or south east asia or asia, western or western asia or europe, eastern or east europe or eastern europe or developing country or developing countries or developing nation?or developing population?or developing world or less developed countr* or less developed nation?or less developed population?or

Table of characteristics of included studies
A Chinese herbal formula shows beneficial effects on comorbid depression and coronary heart disease based on the philosophy of psycho-cardiology China Depression and Coronary Heart disease Xinju 2017 The efficacy of internet-based cognitive behaviour therapy on blood pressure for comorbid hypertension and insomnia China Hypertension and insomnia Xin 2002 A Clinical Trial of Paroxetine and Psychotherapy in Patients with Poststroke Depression and Anxiety China Acute brain stroke, depression, anxiety Freitas Júnior 2010 Estudo comparativo dos efeitos agudos do sildenafil e nitroprussiato de sódio sobre a hipertensão pulmonar de pacientes com insuficiência cardíaca avançada A study on the treatment of depression and anxiety in elderly patients by Shu gan jie yu capsule combined with Ascitalopram China Anxiety, Depression Buranakitjaroen 2007 Efficacy and safety of sildenafil in Asian males with erectile dysfunction and cardiovascular risk Thailand, Malaysia Erectile dysfunction, with one or more of HT, dyslipidaemia, T2DM Vanelle 2006 A double-blind RCT of amisulpride versus olanzapine for 2 months in the treatment of subjects with schizophrenia and comorbid depression France, Italy, and Tunisia.

5: Prevention and Treatment outcomes from outcome generation and Delphi R1 stages, classified using Dodd's taxonomy.
An individual's belief to have the ability to do what is necessary to achieve a desired outcome (e.g., symptom control).The cost of a healthcare service that is paid either by the government, the patient, or their family s view of their emotional, physical, material, and social well-being.It includes the degree to which a person feels they are healthy, comfortable, and able to participate in or enjoy life events.